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Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α

Estrogens are suggested to play a role in the development and progression of proliferative diseases such as breast cancer. Like other steroid hormone receptors, the estrogen receptor-α (ERα) is a substrate of protein kinases, and phosphorylation has profound effects on its function and activity. Giv...

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Autores principales: Medunjanin, Senad, Weinert, Sönke, Schmeisser, Alexander, Mayer, Doris, Braun-Dullaeus, Ruediger C.
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861619/
https://www.ncbi.nlm.nih.gov/pubmed/20219974
http://dx.doi.org/10.1091/mbc.E09-08-0724
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author Medunjanin, Senad
Weinert, Sönke
Schmeisser, Alexander
Mayer, Doris
Braun-Dullaeus, Ruediger C.
author_facet Medunjanin, Senad
Weinert, Sönke
Schmeisser, Alexander
Mayer, Doris
Braun-Dullaeus, Ruediger C.
author_sort Medunjanin, Senad
collection PubMed
description Estrogens are suggested to play a role in the development and progression of proliferative diseases such as breast cancer. Like other steroid hormone receptors, the estrogen receptor-α (ERα) is a substrate of protein kinases, and phosphorylation has profound effects on its function and activity. Given the importance of DNA-dependent protein kinase (DNA-PK) for DNA repair, cell cycle progression, and survival, we hypothesized that it modulates ERα signaling. Here we show that, upon estrogen stimulation, DNA-PK forms a complex with ERα in a breast cancer cell line (MELN). DNA-PK phosphorylates ERα at Ser-118. Phosphorylation resulted in stabilization of ERα protein as inhibition of DNA-PK resulted in its proteasomal degradation. Activation of DNA-PK by double-strand breaks or its inhibition by siRNA technology demonstrated that estrogen-induced ERα activation and cell cycle progression is, at least, partially dependent on DNA-PK.
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spelling pubmed-28616192010-07-16 Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α Medunjanin, Senad Weinert, Sönke Schmeisser, Alexander Mayer, Doris Braun-Dullaeus, Ruediger C. Mol Biol Cell Articles Estrogens are suggested to play a role in the development and progression of proliferative diseases such as breast cancer. Like other steroid hormone receptors, the estrogen receptor-α (ERα) is a substrate of protein kinases, and phosphorylation has profound effects on its function and activity. Given the importance of DNA-dependent protein kinase (DNA-PK) for DNA repair, cell cycle progression, and survival, we hypothesized that it modulates ERα signaling. Here we show that, upon estrogen stimulation, DNA-PK forms a complex with ERα in a breast cancer cell line (MELN). DNA-PK phosphorylates ERα at Ser-118. Phosphorylation resulted in stabilization of ERα protein as inhibition of DNA-PK resulted in its proteasomal degradation. Activation of DNA-PK by double-strand breaks or its inhibition by siRNA technology demonstrated that estrogen-induced ERα activation and cell cycle progression is, at least, partially dependent on DNA-PK. The American Society for Cell Biology 2010-05-01 /pmc/articles/PMC2861619/ /pubmed/20219974 http://dx.doi.org/10.1091/mbc.E09-08-0724 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
Medunjanin, Senad
Weinert, Sönke
Schmeisser, Alexander
Mayer, Doris
Braun-Dullaeus, Ruediger C.
Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α
title Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α
title_full Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α
title_fullStr Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α
title_full_unstemmed Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α
title_short Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α
title_sort interaction of the double-strand break repair kinase dna-pk and estrogen receptor-α
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861619/
https://www.ncbi.nlm.nih.gov/pubmed/20219974
http://dx.doi.org/10.1091/mbc.E09-08-0724
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